Efficacy and safety of apremilast in patients with mild-to-moderate psoriasis up to 32 weeks: Results from the extension phase of the randomized, phase 3 ADVANCE trial
Authors: Linda Stein Gold, Kim Papp, David Pariser, Neal Bhatia, Howard Sofen, Lorne Albrecht, Melinda Gooderham, Kristina Callis Duffin, Mindy Chen, Maria Paris, Sue Cheng, Hernan Picard, Yao Wang, Lawrence Green
Journal: Journal of the American Academy of Dermatology (2022)

To the Editor: Mild-to-moderate psoriasis often involves special areas such as the scalp.1Lebwohl M.G. Bachelez H. Barker J. et al.Patient perspectives in the management of psoriasis: results from the population-based Multinational Assessment of Psoriasis and Psoriatic Arthritis Survey.J Am Acad Dermatol. 2014; 70: 871-881Abstract Full Text Full Text PDF PubMed Scopus (403) Google Scholar Patients can experience substantial quality-of-life impairment despite limited overall skin involvement.1Lebwohl M.G. Bachelez H. Barker J. et al.Patient perspectives in the management of psoriasis: results from the population-based Multinational Assessment of Psoriasis and Psoriatic Arthritis Survey.J Am Acad Dermatol. 2014; 70: 871-881Abstract Full Text Full Text PDF PubMed Scopus (403) Google Scholar In the phase 3 ADVANCE study (NCT03721172), apremilast demonstrated efficacy and tolerability in adults with mild-to-moderate psoriasis (static Physician's Global Assessment [sPGA] 2-3, psoriasis-involved body surface area [BSA] 2%-15%, and Psoriasis Area and Severity Index 2-15) inadequately controlled with/intolerant to ≥1 topical therapy.2Stein Gold L. Papp K. Leonardi C. et al.Efficacy and safety of apremilast in patients with mild to moderate plaque psoriasis: results of a phase 3, multicenter, randomized, double-blind, placebo-controlled trial.J Am Acad Dermatol. 2022; 86: 77-85Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar Patients were randomized 1:1 to apremilast 30 mg BID or placebo for 16 weeks, followed by a 16-week extension phase. We present efficacy and safety of apremilast during the extension phase. Of 595 randomized patients (apremilast: 297; placebo: 298), 84.5% entered (apremilast: 257; placebo: 246) and 73.4% (n = 437) completed the extension phase, including 221 patients continuing apremilast treatment. Of 503 patients, 66 (13.1%) discontinued. The primary endpoint was met: 21.6% of apremilast-treated patients achieved an sPGA score of 0 (clear) or 1 (almost clear) and a ≥2-point reduction from baseline at week 16 vs 4.1% with placebo (P < .0001).2Stein Gold L. Papp K. Leonardi C. et al.Efficacy and safety of apremilast in patients with mild to moderate plaque psoriasis: results of a phase 3, multicenter, randomized, double-blind, placebo-controlled trial.J Am Acad Dermatol. 2022; 86: 77-85Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar At week 32, the sPGA response was maintained by 30.2% (64 of 212) of patients continuing apremilast (apremilast/apremilast) and 34.3% (72 of 210) of patients initially randomized to placebo (placebo/apremilast) using data as observed (DAO); apremilast/apremilast: 24.9% (64 of 257) and placebo/apremilast: 29.3% (72 of 246) using nonresponder imputation. Improvements in secondary endpoints observed at week 16 (Supplementary Material, available via Mendeley at https://data.mendeley.com/datasets/wf4g3yxvzz/1) were sustained up to week 32 in patients continuing apremilast (DAO: BSA-75: 49.1% [104 of 212] [Fig 1]; Whole Body Itch Numeric Rating Scale response: 51.9% [95 of 183] and 62.1% [110 of 177] [Supplementary Fig 1, available via Mendeley at https://data.mendeley.com/datasets/wf4g3yxvzz/1]; Scalp Physician's Global Assessment response: 49.7% [78 of 157] and 58.6% [78 of 133]; Dermatology Life Quality Index: –5.8 [n = 212] and –6.7 [n = 207] [Supplementary Fig 2, available via Mendeley at https://data.mendeley.com/datasets/wf4g3yxvzz/1]). At week 32, 29.3% of patients continuing apremilast achieved Psoriasis Area and Severity Index-75, comparable to the 27.2% of patients who switched from placebo to apremilast (nonresponder imputation; Fig 2). BSA-75, Whole Body Itch Numeric Rating Scale, and Scalp Physician's Global Assessment responses at week 32 analyzed with nonresponder imputation were consistent with DAO (Supplementary Fig 3, available via Mendeley at https://data.mendeley.com/datasets/wf4g3yxvzz/1).Fig 2Proportions of patients with psoriasis achieving PASI-75 response based on NRI analysis. Bars represent two-sided 95% CIs. NRI, Nonresponder imputation; PASI, Psoriasis Area and Severity Index; PASI-75, ≥75% reduction from baseline in PASI score.View Large Image Figure ViewerDownload Hi-res image Download (PPT) During the apremilast-exposure period (0-32 weeks), 544 patients received ≥1 apremilast dose (total apremilast exposure: 234.3 person-years). Most (93.2%) patients with treatment-emergent adverse events during this period had mild/moderate treatment-emergent adverse events. The most common treatment-emergent adverse events (≥5%) were diarrhea (14.3%, 78 of 544), headache (12.9%, 70 of 544), nausea (12.7%, 69 of 544), upper respiratory tract infection (8.5%, 46 of 544), and nasopharyngitis (6.8%, 37 of 544), consistent with the known apremilast safety profile.3Papp K. Reich K. Leonardi C.L. et al.Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM 1]).J Am Acad Dermatol. 2015; 73: 37-49Abstract Full Text Full Text PDF PubMed Scopus (448) Google Scholar,4Paul C. Cather J. Gooderham M. et al.Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate to severe plaque psoriasis over 52 weeks: a phase III, randomized, controlled trial (ESTEEM 2).Br J Dermatol. 2015; 173: 1387-1399Crossref PubMed Scopus (345) Google Scholar Although topical therapies are commonly prescribed for mild-to-moderate psoriasis, systemic treatment may benefit patients with intractable pruritus or special area involvement (eg, the scalp).5Menter A. Strober B.E. Kaplan D.H. et al.Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics.J Am Acad Dermatol. 2019; 80: 1029-1072Abstract Full Text Full Text PDF PubMed Scopus (498) Google Scholar Bothersome symptoms and psoriasis locations can impair quality of life.1Lebwohl M.G. Bachelez H. Barker J. et al.Patient perspectives in the management of psoriasis: results from the population-based Multinational Assessment of Psoriasis and Psoriatic Arthritis Survey.J Am Acad Dermatol. 2014; 70: 871-881Abstract Full Text Full Text PDF PubMed Scopus (403) Google Scholar Per current guidelines, mild-to-moderate psoriasis may require systemic treatment in patients with high disease burden or psoriasis inadequately controlled with topicals. Efficacy results may be biased by lack of an active comparator and reporting DAO findings. Improvements in sPGA, BSA, whole-body itch Numeric Rating Scale, Scalp Physician's Global Assessment, and Dermatology Life Quality Index were maintained through week 32 with apremilast treatment. These findings demonstrate that continued apremilast treatment results in sustained clinical improvements in overall disease severity, scalp psoriasis, itch, and quality of life for patients with mild-to-moderate psoriasis. Qualified researchers may request data from Amgen clinical studies. Complete details are available at http://www.amgen.com/datasharing. Linda Stein Gold has received honoraria, grants, and/or research funding as a speaker, investigator, and/or advisory board member for AbbVie, Amgen Inc, Arcutis, Celgene Corporation, Dermira, Dermavant, Eli Lilly, Galderma, LEO Pharma, Novartis, Pfizer, Regeneron, Sanofi Genzyme, UCB, and Valeant. Kim Papp has received honoraria, grants, and/or research funding as a speaker, investigator, advisory board member, data safety monitoring board member, and/or consultant for AbbVie, Actelion, Amgen Inc, Astellas Pharma US, Boehringer Ingelheim, Bausch Health, Celgene Corporation, Dermira, Dow Pharmaceuticals, Eli Lilly, Frontier, Galderma, Janssen, Kyowa Hakko Kirin Pharma, LEO Pharma, MedImmune, Merck & Co, Inc, Novartis, Pfizer, Regeneron, Roche Laboratories, Sanofi Genzyme, Takeda Pharmaceuticals, UCB, and Valeant and is a steering committee member for PSLOAR, PURE. David Pariser is a honoraria, investigator, advisory board, or data monitoring board member for Amgen Inc, AO Biome, Asana, Brickel Biotech, Celgene Corporation, Dermavant, Dermira, Eli Lilly, Menlo Therapeutics, Merck, Novartis, Ortho, Regeneron, Atacama, Biofrontera, Bristol Myers Squibb, LEO Pharma, Pfizer, Sanofi, and Valeant. Neal Bhatia is an advisor, consultant, investigator, and/or speaker for AbbVie, Actavis, Allergan, Amgen Inc, Aqua, Bayer, Biofrontera, BioPharmX, Castle, Cipher, Dermira, Encore, Exeltis, Ferndale, Foamix, Galderma, Intraderm, ISDIN, LaRoche-Posay, LEO Pharma, Novan, Novartis, PharmaDerm, Pfizer, Promius, Regeneron, Sanofi, Sun Pharma, and Valeant. Howard Sofen has received honoraria, grants, and/or research funding as an investigator and/or advisory board member for AbbVie, Amgen Inc, Celgene Corporation, Dermira, Dermavant, Eli Lilly, Galderma, LEO Pharma, Novartis, Pfizer, and UCB. Lorne Albrecht has received honoraria, grants, and/or research funding as a speaker, investigator, advisory board member, and/or consultant for AbbVie, Amgen Inc, Arcutis, Boehringer Ingelheim, Bausch Health/Valeant, Celgene Corporation, Dermira, Dermavant, Eli Lilly, Galderma, Janssen, LEO Pharma, MedImmune, Merck & Co, Novartis, Pfizer, Regeneron, Roche Laboratories, Sanofi Genzyme, and UCB. Melinda Gooderham has received honoraria, grants, and/or research funding as a speaker, investigator, advisory board member, data safety monitoring board member, and/or consultant AbbVie, Amgen Inc, Akros, Arcutis, Bausch/Valeant, Boehringer Ingelheim, Celgene Corporation, Dermira, Dermavant, Eli Lilly, Galderma, Janssen, Kyowa Hakko Kirin Pharma, LEO Pharma, MedImmune, Merck & Co, Novartis, Pfizer, Regeneron, Roche Laboratories, Sanofi Genzyme, Takeda Pharmaceuticals USA Inc, and UCB. Mindy Chen, Maria Paris, Sue Cheng, and Hernan Picard are employees and stockholders for Amgen Inc. Yao Wang was employed at time of study. Kristina Callis Duffin has received honoraria, grants, and/or research funding as investigator, advisory board member, consultant, and nonpromotional speaker for Novartis and has received honoraria, grants, and/or research funding as an investigator, advisory board member, and/or consultant for AbbVie, Amgen Inc, Boehringer Ingelheim, Celgene Corporation, Eli Lilly, Janssen, Novartis, Pfizer, Regeneron, and UCB. Lawrence Green is an investigator, speaker, and/or consultant for AbbVie, Amgen Inc, Arcutis, Dermavant, MC2, Novartis, Lilly, OrthoDerm, Sun Pharma, and UCB. Writing support was funded by Amgen and provided by Kristin Carlin, BSPharm, MBA, of Peloton Advantage, LLC, an OPEN Health company, and Dawn Nicewarner, PhD, employee of and stockholder in Amgen Inc.